TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14307	43144;43145;43146	chr2:178633440;178633439;178633438	chr2:179498167;179498166;179498165
N2AB	12666	38221;38222;38223	chr2:178633440;178633439;178633438	chr2:179498167;179498166;179498165
N2A	11739	35440;35441;35442	chr2:178633440;178633439;178633438	chr2:179498167;179498166;179498165
N2B	5242	15949;15950;15951	chr2:178633440;178633439;178633438	chr2:179498167;179498166;179498165
Novex-1	5367	16324;16325;16326	chr2:178633440;178633439;178633438	chr2:179498167;179498166;179498165
Novex-2	5434	16525;16526;16527	chr2:178633440;178633439;178633438	chr2:179498167;179498166;179498165
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-93
• Domain position: 77
• Structural Position: 163
• Q(SASA): 0.4173
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
K/T	None	None	None	N	0.245	0.173	0.166414681773	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
K/A	0.1579	likely_benign	0.154	benign	-0.739	Destabilizing	0.035	N	0.488	neutral	None	None	None	None	N
K/C	0.57	likely_pathogenic	0.5523	ambiguous	-0.62	Destabilizing	0.824	D	0.515	neutral	None	None	None	None	N
K/D	0.4466	ambiguous	0.4305	ambiguous	-0.17	Destabilizing	0.149	N	0.561	neutral	None	None	None	None	N
K/E	0.1056	likely_benign	0.0998	benign	-0.041	Destabilizing	0.062	N	0.569	neutral	N	0.502526981	None	None	N
K/F	0.5501	ambiguous	0.5271	ambiguous	-0.384	Destabilizing	0.38	N	0.549	neutral	None	None	None	None	N
K/G	0.3363	likely_benign	0.3318	benign	-1.126	Destabilizing	0.149	N	0.535	neutral	None	None	None	None	N
K/H	0.2349	likely_benign	0.2318	benign	-1.472	Destabilizing	0.38	N	0.558	neutral	None	None	None	None	N
K/I	0.1661	likely_benign	0.1482	benign	0.274	Stabilizing	0.096	N	0.572	neutral	None	None	None	None	N
K/L	0.1898	likely_benign	0.1864	benign	0.274	Stabilizing	0.081	N	0.533	neutral	None	None	None	None	N
K/M	0.1086	likely_benign	0.1066	benign	0.189	Stabilizing	0.317	N	0.567	neutral	D	0.600053003	None	None	N
K/N	0.2023	likely_benign	0.1974	benign	-0.563	Destabilizing	0.117	N	0.575	neutral	D	0.575708036	None	None	N
K/P	0.7388	likely_pathogenic	0.7569	pathogenic	-0.034	Destabilizing	0.555	D	0.607	neutral	None	None	None	None	N
K/Q	0.0865	likely_benign	0.0863	benign	-0.586	Destabilizing	0.001	N	0.283	neutral	N	0.508941464	None	None	N
K/R	0.0865	likely_benign	0.0851	benign	-0.687	Destabilizing	None	N	0.287	neutral	N	0.514708636	None	None	N
K/S	0.1855	likely_benign	0.1841	benign	-1.24	Destabilizing	0.007	N	0.268	neutral	None	None	None	None	N
K/T	0.0522	likely_benign	0.0516	benign	-0.89	Destabilizing	None	N	0.245	neutral	N	0.50391117	None	None	N
K/V	0.163	likely_benign	0.1478	benign	-0.034	Destabilizing	0.001	N	0.367	neutral	None	None	None	None	N
K/W	0.6989	likely_pathogenic	0.7114	pathogenic	-0.254	Destabilizing	0.935	D	0.567	neutral	None	None	None	None	N
K/Y	0.459	ambiguous	0.4305	ambiguous	0.026	Stabilizing	0.555	D	0.549	neutral	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.